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 Journal of Steroid Biochemistry and Molecular Biology 204 (2020) 105771

Contents lists available at ScienceDirect

Journal of Steroid Biochemistry and Molecular Biology

journal homepage: www.elsevier.com/locate/jsbmb

Vitamin D and survival in COVID-19 patients: A quasi-experimental study

Cédric Annweiler a, b, c, *, Bérangère Hanotte d, Claire Grandin de l’Eprevier e,
Jean-Marc Sabatier f, Ludovic Lafaie d, Thomas Célarier d, g, h
a
Department of Geriatric Medicine and Memory Clinic, Research Center on Autonomy and Longevity, University Hospital, Angers, France
b
UPRES EA 4638, University of Angers, Angers, France
c
Robarts Research Institute, Department of Medical Biophysics, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON, Canada
d
Department of Clinical Gerontology, University Hospital of Saint-Etienne, Saint-Etienne, France
e
Geriatric Hospital of Saint Laurent de Chamousset, Saint Laurent de Chamousset, France
f
Université Aix-Marseille, Institut de Neuro-Physiopathologie (INP), UMR 7051, Faculté de Pharmacie, 27 Bd Jean Moulin, 13385, Marseille Cedex, France
g
Chaire Santé des Ainés, University of Jean Monnet, Saint-Etienne, France
h
Gérontopôle Auvergne-Rhône-Alpes, Saint-Etienne, France

A R T I C L E I N F O A B S T R A C T

Keywords: Vitamin D may be a central biological determinant of COVID-19 outcomes. The objective of this quasi-
COVID-19 experimental study was to determine whether bolus vitamin D3 supplementation taken during or just before
SARS-CoV-2 COVID-19 was effective in improving survival among frail elderly nursing-home residents with COVID-19. Sixty-
Vitamin D
six residents with COVID-19 from a French nursing-home were included in this quasi-experimental study. The
Therapeutics
Quasi-experimental study
“Intervention group” was defined as those having received bolus vitamin D3 supplementation during COVID-19
Older adults or in the preceding month, and the “Comparator group” corresponded to all other participants. The primary and
secondary outcomes were COVID-19 mortality and Ordinal Scale for Clinical Improvement (OSCI) score in acute
phase, respectively. Age, gender, number of drugs daily taken, functional abilities, albuminemia, use of corti­
costeroids and/or hydroxychloroquine and/or antibiotics (i.e., azithromycin or rovamycin), and hospitalization
for COVID-19 were used as potential confounders. The Intervention (n = 57; mean ± SD, 87.7 ± 9.3years; 79 %
women) and Comparator (n = 9; mean, 87.4 ± 7.2years; 67 %women) groups were comparable at baseline, as
were the COVID-19 severity and the use of dedicated COVID-19 drugs. The mean follow-up time was 36 ± 17
days. 82.5 % of participants in the Intervention group survived COVID-19, compared to only 44.4 % in the
Comparator group (P = 0.023). The full-adjusted hazard ratio for mortality according to vitamin D3 supple­
mentation was HR = 0.11 [95 %CI:0.03;0.48], P = 0.003. Kaplan-Meier distributions showed that Intervention
group had longer survival time than Comparator group (log-rank P = 0.002). Finally, vitamin D3 supplemen­
tation was inversely associated with OSCI score for COVID-19 (β=-3.84 [95 %CI:-6.07;-1.62], P = 0.001). In
conclusion, bolus vitamin D3 supplementation during or just before COVID-19 was associated in frail elderly
with less severe COVID-19 and better survival rate.

1. Introduction patterns through their effects on gene expression [2]. In particular, by

Since December 2019, the COVID-19 caused by SARS-CoV-2 is
spreading worldwide from China, affecting millions of people and
leaving thousands of dead, mostly in older adults. With the lack of
effective therapy, chemoprevention and vaccination [1], focusing on the
immediate repurposing of existing drugs gives hope of curbing the
pandemic. Importantly, a most recent genomics-guided tracing of the
SARS-CoV-2 targets in human cells identified vitamin D among the three
top-scoring molecules manifesting potential infection mitigation
activating or repressing several genes in the promoter region of which it
binds to the vitamin D response element [3], vitamin D may theoreti­
cally prevent or improve COVID-19 adverse outcomes by regulating (i)
the renin-angiotensin system (RAS), (ii) the innate and adaptive cellular
immunity, and (iii) the physical barriers [4]. Consistently, epidemiology
shows that hypovitaminosis D is more common from October to March
at northern latitudes above 20 degrees [3], which corresponds precisely
to the latitudes with the highest lethality rates of COVID-19 during the
first months of winter 2020 [1]. In line with this, significant inverse

* Corresponding author at: Department of Geriatric Medicine, Angers University Hospital, F-49933, Angers, France.
E-mail address: Cedric.Annweiler@chu-angers.fr (C. Annweiler).

https://doi.org/10.1016/j.jsbmb.2020.105771
Received 7 July 2020; Accepted 28 September 2020
Available online 13 October 2020
0960-0760/© 2020 Elsevier Ltd. All rights reserved.
C. Annweiler et al.
associations were found in 20 European countries between serum
25-hydroxyvitamin D (25(OH)D) concentration and the number of
COVID-19 cases, as well as with COVID-19 mortality [5]. This suggests
that increasing serum 25(OH)D concentration may improve the prog­
nosis of COVID-19. However, no randomized controlled trial (RCT) has
tested the effect of vitamin D supplements on COVID-19 outcomes yet.
We had the opportunity to examine the association between the use of
vitamin D3 supplements and COVID-19 mortality in a sample of frail
elderly nursing-home residents infected with SARS-CoV-2. The main
objective of this quasi-experimental study was to determine whether
bolus vitamin D3 supplementation taken during or just before COVID-19
was effective in improving survival among frail elderly COVID-19 pa­
tients living in nursing-home. The secondary objective was to determine
whether this intervention was effective in limiting the clinical severity of
the infection.
2. Material and methods
2.1. Study population
The study consisted in a quasi-experimental study in a middle-sized
nursing-home in Rhône, South-East of France, the residents of which
were largely affected by COVID-19 in March-April 2020 (N = 96,
including n = 66 with COVID-19). Data were retrospectively collected
from the residents’ records of the nursing-home.
The nursing-home is dedicated to residents with physical disabilities,
major neurocognitive and psychiatric disorders. The facility includes 56
single rooms and 21 double rooms, along with communal dining and
activity areas. There are no closed units. All residents were allowed to
move around the building until 21 March 2020, when social distancing
and other preventive measures were implemented. Residents were iso­
lated in their rooms with no communal meals or group activities. No
visitors, including families, were allowed in the nursing-home since 10
March 2020. Enhanced hygiene measures were implemented, including
cleaning and disinfection of frequently touched surfaces, permanent face
masks, and additional hand hygiene stations for staff members.
The inclusion criteria for the present analysis were as follows: 1)
residents with clinically obvious or diagnosed COVID-19 with RT-PCR in
March-April 2020; 2) data available on the treatments received,
including vitamin D supplementation, since the diagnosis of COVID-19
and during the previous month at least; 3) data available on the vital
status and COVID-19 evolution as of May 15, 2020; 4) no objection from
the resident and/or relatives to the use of anonymized clinical and
biological data for research purposes. Sixty-six residents had COVID-19
during the study period. They all met the other inclusion criteria and
were included in the present analysis.
2.2. Intervention: bolus vitamin D3 supplementation during or just before
COVID-19
All residents in the nursing-home receive chronic vitamin D sup­
plementation with regular maintenance boluses (single oral dose of
80,000 IU vitamin D3 every 2–3 months), without systematically per­
forming serum control test as recommended in French nursing-homes
[6] due to the very high prevalence of hypovitaminosis D reaching
90–100 % in this population [7]. Here, the "Intervention group" was
defined as all COVID-19 residents who received an oral bolus of 80,000
IU vitamin D3 either in the week following the suspicion or diagnosis of
COVID-19, or during the previous month. The "Comparator group"
corresponded to all other COVID-19 residents who did not receive any
recent vitamin D supplementation. None received D2 or intramuscular
supplements. All medications were dispended and supervised by a nurse.
2.3. Primary outcome: COVID-19 mortality
The primary outcome was mortality of COVID-19 residents during
2
Journal of Steroid Biochemistry and Molecular Biology 204 (2020) 105771
follow-up. Follow-up started from the day of COVID-19 diagnosis for
each patient, and continued until May 15, 2020, or until death if
applicable.
2.4. Secondary outcome: OSCI score for COVID-19 in acute phase
The secondary outcome was the score on the World Health Organi­
zation’s Ordinal Scale for Clinical Improvement (OSCI) for COVID-19
[8]. The score was calculated by the geriatrician of the nursing-home
during the most severe acute phase of COVID-19 for each patient. The
OSCI distinguishes between several levels of COVID-19 clinical severity
according to the outcomes and dedicated treatments required, with a
score ranging from 0 (benign) to 8 (death). A score of 4 corresponds to
the introduction of oxygen (nasal oxygen catheter or oral nasal mask),
and a score of 6 to intubation and invasive ventilation [8].
2.5. Covariables
Age, gender, number of drugs daily taken, functional abilities,
nutritional status, COVID-19 treatment with corticosteroids and/or
hydroxychloroquine and/or dedicated antibiotics, and hospitalization
for COVID-19 were used as potential confounders. The number of drugs
usually taken per day was recovered from prescriptions in the nursing-
home and served as a measure of the burden of disease, as previously
reported [9]. The use of corticosteroids and/or hydroxychloroquine
and/or dedicated antibiotics (i.e., azithromycin or rovamycin) were
noted from prescriptions in the nursing-home or during hospitalization,
as appropriate. Functional abilities prior to COVID-19 were measured
from 1 to 6 (best) with the Iso-Resources Groups (GIR) [10]. Finally, the
prognosis related to the nutritional status prior to COVID-19 was eval­
uated using the last measure of serum albumin concentration during the
past semester, as appropriate [11].
2.6. Statistical analysis
Participants’ characteristics were summarized using means and
standard deviations (SD) or frequencies and percentages, as appropriate.
As the number of observations was higher than 40, comparisons were
not affected by the shape of the error distribution and no transform was
applied [12]. First, comparisons between participants separated into
Intervention and Comparator groups were performed using
Mann-Whitney U test or the Chi-square test or Fisher test, as appro­
priate; and then according to mortality. Secondly, a full-adjusted Cox
regression was used to examine the associations of mortality (dependent
variable) with bolus vitamin D3 supplements and covariables (inde­
pendent variables). The model produces a survival function that pro­
vides the probability of death at a given time for the characteristics
supplied for the independent variables. Third, the elapsed time to death
was studied by survival curves computed according to Kaplan-Meier
method and compared by log-rank test. Finally, univariate and multi­
ple linear regressions were used to examine the association of bolus
vitamin D3 supplementation (independent variable) with OSCI score
(dependent variable), while adjusting for potential confounders. P-val­
ues<0.05 were considered significant. All statistics were performed
using SPSS (v23.0, IBM Corporation, Chicago, IL) and SAS® version 9.4
software (Sas Institute Inc).
2.7. Standard protocol approvals, registrations, and patient consents
The study was conducted in accordance with the ethical standards
set forth in the Helsinki Declaration (1983). No participant or relatives
objected to the use of anonymized clinical and biological data for
research purposes. The study was approved by the Ethical Committee of
Angers University Hospital (2020/67). The study protocol was also
declared to the National Commission for Information technology and
civil Liberties (CNIL, number 202000081).
C. Annweiler et al. Journal of Steroid Biochemistry and Molecular Biology 204 (2020) 105771

3. Results
Sixty-six participants (mean ± SD age 87.7 ± 9.0years, range
63− 103years; 77.3 % women) were infected with SARS-CoV-2 and
included in this quasi-experimental study. The mean follow-up was 36 ±
17days. Fifty-one people survived COVID-19, while 15 died. The two
groups were comparable at baseline with no significant difference
regarding the age (P = 0.699), gender (P = 0.731), the mean number of
drugs usually taken per day (P = 0.053), the GIR score (P = 0.209) and
the serum albumin concentration (P = 0.263) (Table 1). Regarding care
dedicated to COVID-19, only the proportion of patients who received a
bolus of vitamin D3 during or just before COVID-19 differed between
deceased participants and survivors, with a higher prevalence in survi­
vors (respectively 92.2 % versus 66.7 %, P = 0.023). In contrast, there
was no between-group difference in the proportion of patients treated
with corticosteroids, hydroxychloroquine or dedicated antibiotics, or
hospitalized for COVID-19.
Table 1 indicates the characteristics of participants separated into
Intervention (n = 57) and Comparator (n = 9) groups. Their baseline
characteristics (age, gender, albuminemia) did not differ between
groups, with the exception of the number of drugs usually taken (which
involved the use of vitamin D supplements) and the disability score
(Table 1). Similarly, the proportion of participants at each OSCI severity
level as well as the use of dedicated COVID-19 drugs did not differ be­
tween Intervention and Comparator groups. At the end of the follow-up,
82.5 % of patients from the Intervention group survived COVID-19,
compared to only 44.4 % in the Comparator group (P = 0.023).
Fig. 1 shows a statistically significant and clinically relevant pro­
tective effect against mortality of bolus vitamin D3 supplementation
received during or just before COVID-19. The hazard ratio (HR) for
mortality according to vitamin D3 supplementation was 0.21 [95 %
confidence interval (95 %CI): 0.07;0.63] P = 0.005 in the unadjusted
model, and HR = 0.11 [95 %CI: 0.03;0.48] P = 0.003 after adjustment
for all potential confounders. No other covariables were associated with
mortality, in particular no other dedicated treatments. Using the season
of the COVID-19 diagnosis as an additional potential confounder did not
affect the results (data not shown). Consistently, Kaplan-Meier distri­
butions showed in Fig. 2 that the residents who had not recently
received vitamin D3 supplements had shorter survival time than those
having received vitamin D3 supplementation during or just before
COVID-19 (log-rank P = 0.002).
Finally, the linear regression model illustrated in Table 2 showed
that bolus vitamin D3 supplementation during or just before COVID-19
was inversely associated with the OSCI score for COVID-19 in acute
phase. Similar results were found before (β=-2.96 [95 %CI: -4.79;-1.12],
P = 0.002) and after adjusting the analyses for potential confounders
(β=-3.84 [95 %CI: -6.07;-1.62], P = 0.001).
4. Discussion
The main finding of this nursing-home-based quasi-experimental
study is that, irrespective of all measured potential confounders, bolus
vitamin D3 supplementation during or just before COVID-19 was asso­
ciated with less severe COVID-19 and better survival rate in frail elderly.
No other treatment showed protective effect. This novel finding provides
a scientific basis for vitamin D replacement trials attempting to improve
COVID-19 prognosis.
To our knowledge we provide here the first quasi-experimental data
examining the effect of vitamin D supplementation on the survival rate
of COVID-19 patients. To date, only rare observational data, all of which
are consistent, are available on the link between vitamin D and COVID-
19. The first reports in COVID-19 patients indicated that adults with
hypovitaminosis D are at greater risk of being infected with SARS-CoV-2
(RR = 1.77 with P < 0.02) [13], and that serum 25(OH)D concentrations
are lower in COVID-19 patients compared to controls [14]. Similarly,
significant inverse correlations were found in 20 European countries
between the mean serum 25(OH)D concentrations and the number of
COVID-19 cases, as well as with mortality [5]. The severity of hypo­
vitaminosis D appears to relate to the prognosis of COVID-19 since, in
the event of COVID-19, exhibiting hypovitaminosis D was associated
with greater risks of having severe COVID-19 (OR = 1.95 with
P = 0.029), of being hospitalized (OR = 1.77 with P = 0.026) and with a

Table 1
Characteristics and comparison of COVID-19 participants (n = 66) according to the study arm.
Study arm
All COVID-19 participants (n = 66) P-value
Comparator group* (n = 9) Intervention group* (n = 57)

Baseline data
Age (years), mean ± SD 87.7 ± 9.0 87.4 ± 7.2 87.7 ± 9.3 0.660
Female gender 51 (77.3) 6 (66.7) 45 (78.9) 0.414
Number of drugs usually taken per day, mean ± SD 7±2 5±2 7±2 0.043
GIR score (/6), mean ± SD 2±1 1 ± 0.4 2±1 0.003
Serum albumin concentration† (g/L), mean ± SD 34.2 ± 5.2 35.4 ± 2.5 34.1 ± 5.4 0.250
COVID-19
Dedicated treatments
Use of corticosteroids 4 (6.1) 1 (11.1) 3 (5.3) 0.452
Use of hydroxychloroquine 2 (3.0) 0 (0.0) 2 (3.5) 1.000
Use of dedicated antibiotics 34 (51.5) 3 (33.3) 21 (54.4) 0.297
Hospitalization for COVID-19 4 (6.1) 0 (0.0) 4 (7.0) 1.000
Outcomes
OSCI score for COVID-19 in acute phase 0.133
OSCI 0 1 (1.5) 0 (0.0) 1 (1.8)
OSCI 1 22 (33.3) 1 (11.1) 21 (37.5)
OSCI 2 19 (28.8) 1 (11.1) 18 (32.1)
OSCI 3 1 (1.5) 0 (0.0) 1 (1.8)
OSCI 4 5 (7.6) 1 (11.1) 4 (7.1)
OSCI 5 3 (4.5) 1 (11.1) 2 (3.6)
OSCI 6 0 (0) 0 (0) 0 (0)
OSCI 7 0 (0) 0 (0) 0 (0)
OSCI 8 15 (22.7) 5 (55.6) 10 (17.5)
Mortality 15 (22.7) 5 (55.6) 10 (17.5) 0.023
Follow-up after COVID-19 diagnosis‡ (days), mean ± SD 36 ± 17 20.9 ± 14.3 38.9 ± 15.6 0.002

Data presented as n (%) where applicable; COVID-19: Coronavirus Disease 2019; GIR: Iso Resource Groups; OSCI: Ordinal Scale for Clinical Improvement of the World
Health Organization; *: “Intervention group” defined as COVID-19 patients having received a bolus of vitamin D3 supplement during COVID-19 or in the preceding
month; †: measured in preceding 6 months; ‡: data were censored at the time of data cutoff (15 May 2020) or until death, as appropriate.

3
C. Annweiler et al. Journal of Steroid Biochemistry and Molecular Biology 204 (2020) 105771

Fig. 1. Hazard ratio for mortality in frail elderly COVID-19 patients according to the use of bolus vitamin D3 supplements during or just before COVID-19, adjusted
for potential confounders (n = 66).
CI: confidence interval; COVID-19: Coronavirus Disease 2019; GIR: Iso Resource Groups; *: measured in preceding 6 months.

Fig. 2. Kaplan-Meier estimates of the cumulative probability of participants’ survival according to the use of bolus vitamin D3 supplements during or just before
COVID-19 (n = 66).

longer hospital stay (β = 0.47 with P < 0.001) [15]. Finally, hypo­
vitaminosis D was found to be associated with greater COVID-19 mor­
tality risk (IRR = 1.56 with P < 0.001 if vitamin D deficiency; P = 0.404
after adjustment) [16]. These results suggest that increasing serum 25
(OH)D concentration may improve the prognosis of COVID-19. Inter­
ventional studies dedicated to COVID-19 are yet warranted for investi­
gating the role of vitamin D supplementation on COVID-19 outcomes.
Interestingly, previous meta-analyses found that high-dose prophylactic
vitamin D supplementation was able to reduce the risk of respiratory
tract infections [17]. Based on this observation, we and others are
conducting an RCT designed to test the effect of high-dose versus
standard-dose vitamin D3 on 14-day mortality in COVID-19 older pa­
tients (https://clinicaltrials.gov/ct2/show/NCT04344041). While
waiting for the recruitment of this RCT to be completed, the findings of
the present quasi-experimental study strongly suggest a benefit of bolus
vitamin D3 supplementation on COVID-19 outcomes and survival.
How vitamin D supplementation may improve COVID-19 outcomes
and survival is not fully elucidated. Three mechanisms are possible:
regulation of (i) the RAS, (ii) the innate and adaptive cellular immunity,
and (iii) the physical barriers [4]. First, vitamin D reduces pulmonary
permeability in animal models of acute respiratory distress syndrome
(ARDS) by modulating the activity of RAS and the expression of the
angiotensin-2 converting enzyme (ACE2) [18]. This action is crucial
since SARS-CoV-2 reportedly uses ACE2 as a receptor to infect host cells
[19] and downregulates ACE2 expression [20]. ACE2 is expressed in
many organs, including the endothelium and the pulmonary alveolar
epithelial cells, where it has protective effects against inflammation
[21]. During COVID-19, downregulation of ACE2 results in an inflam­
matory chain reaction, the cytokine storm, complicated by ARDS [22].
In contrast, a study in rats with chemically-induced ARDS showed that
the administration of vitamin D increased the levels of ACE2 mRNA and
proteins [23]. Rats supplemented with vitamin D had milder ARDS
symptoms and moderate lung damage compared to controls. Second,
many studies have described the antiviral effects of vitamin D, which
works either by induction of antimicrobial peptides with direct antiviral
activity against enveloped and non-enveloped viruses, or by immuno­
modulatory and anti-inflammatory effects [24]. These are potentially
important during COVID-19 to limit the cytokine storm. Vitamin D can
prevent ARDS [25] by reducing the production of pro-inflammatory Th1
cytokines, such as TNFα and interferon γ [24]. It also increases the
expression of anti-inflammatory cytokines by macrophages [24]. Third,
vitamin D stabilizes physical barriers [4]. These barriers are made up of
closely linked cells to prevent outside agents (such as viruses) from
reaching tissues susceptible to viral infection. Although viruses alter the

4
C. Annweiler et al. Journal of Steroid Biochemistry and Molecular Biology 204 (2020) 105771

Table 2 5. Conclusions
Univariate and multiple linear regressions showing the association of the use of
bolus vitamin D3 supplements during or just before COVID-19 (independent In conclusion, we were able to report among frail elderly residents
variable) with the OSCI score for COVID-19 in acute phase (dependent variable), that bolus vitamin D3 supplementation taken during or just before
adjusted for participants’ characteristics (n = 66). COVID-19 was associated with less severe COVID-19 and better survival
OSCI score for COVID-19 in acute phase rate. No other treatment showed protective effect.
Unadjusted model Full-adjusted model Vitamin D3 supplementation may represent an effective, accessible
and well-tolerated treatment for COVID-19, the incidence of which in­
Unadjusted β P- Full-adjusted P-
[95 % CI] value β [95 % CI] value creases dramatically and for which there are currently no treatments.
Further prospective, preferentially interventional, studies are needed to
Bolus vitamin D3 − 2.96 0.002 − 3.84 [-6.07;- 0.001
supplementation during [-4.79;-1.12] 1.62]
confirm whether supplementing older adults with bolus vitamin D3
or just before COVID-19 during or just before the infection could improve, or prevent, COVID-19.
Age 0.02 0.563 0.04 0.400
[-0.05;0.10] [-0.05;0.12]
Sponsor’s role
Female gender − 0.13 0.870 0.36 0.687
[-1.76;1.49] [-1.41;2.12]
Number of drugs usually − 0.26 0.070 − 0.18 0.273 No sources of funding were used to assist in this study.
taken per day [-0.54;0.02] [-0.51;0.15]
GIR score − 0.28 0.333 0.21 0.617
Authors contribution
[-0.86;0.30] [-0.48;0.89]
Serum albumin 0.03 0.647 − 0.001 0.993
concentration* [-0.11;0.17] [-0.15;0.15] - CA has full access to all of the data in the study, takes responsibility
Use of corticosteroids 2.41 0.087 3.53 0.033 for the data, the analyses and interpretation and has the right to
[-0.36;5.20] [0.30;6.75]
publish any and all data, separate and apart from the attitudes of the
Use of hydroxychloroquine 1.83 0.357 2.49 0.226
[-2.11;5.76] [-1.59;6.57] sponsors. All authors have read and approved the manuscript.
Use of dedicated antibiotics − 0.22 0.746 − 0.56 0.503 - Study concept and design: CA, BH, CGE, JMS, LL and TC.
[-1.59;1.14] [-2.21;1.10] - Acquisition of data: BH and CGE.
Hospitalization for COVID- 1.09 0.446 0.72 0.652 - Analysis and interpretation of data: CA and TC.
19 [-1.75;3.92] [-2.48;3.93]
- Drafting of the manuscript: CA.
β: coefficient of regression corresponding to a change in OSCI score for COVID- - Critical revision of the manuscript for important intellectual content:
19 in acute phase (/8); CI: confidence interval; COVID-19: Coronavirus Disease BH, CGE, JMS, LL and TC.
2019; GIR: Iso Resource Groups; OSCI: Ordinal Scale for Clinical Improvement of - Obtained funding: Not applicable.
the World Health Organization; *: measured in preceding 6 months. - Statistical expertise: CA.
- Administrative, technical, or material support: CA and TC.
integrity of the cell junction, vitamin D contributes to the maintenance - Study supervision: CA.
of functional tight junctions via E-cadherin [4]. All these antiviral effects
could potentiate each other and explain our results.
We also found that none of the other dedicated drugs used in this Declaration of Competing Interest
quasi-experimental study was associated with better survival rate in
COVID-19 patients. The interest of these drugs in COVID-19 is still The authors report no declarations of interest.
debated, whether for hydroxychloroquine [26] or azithromycin [27]
even if the administration of systemic corticosteroids has shown some Acknowledgments
interest on mortality risk in critically ill patients with COVID-19 [28].
However, it should be noted that these drugs were given here as part of The authors wish to thank their collaborators:
patient care in the most advanced and severe clinical situations, which - Angeline MEY, MD, from the Department of Clinical Gerontology,
could have biased and masked their effectiveness (if any). University Hospital of Saint-Etienne, Saint-Etienne, France;
The strengths of the present study include i) the originality of the - Pauline GUILLEMIN, MD, from the Geriatric Hospital of Saint
research question on an emerging infection for which there is no vali­ Symphorien sur Coise, Saint Symporien sur Coise, France;
dated treatment, ii) the detailed description of the participants’ char­ - Jennifer GAUTIER, MS, from the Research Center on Autonomy and
acteristics allowing the use of multivariate models to measure adjusted Longevity, University Hospital, Angers, France.
associations, and iii) the standardized collection of data from a single There was no compensation for their contribution.
research center.
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